The correlation between No. 6 and No. 14v lymph node metastasis and the value of dissecting these lymph nodes in radical gastrectomy / 中华胃肠外科杂志

Radical gastrectomy with D2 lymphadenectomy has been widely performed as the standard surgery for patients with gastric cancer in major medical centers in China and abroad. However, the exact extent of lymph node dissection is still controversial. In the latest version of the Japanese Gastric Cancer Treatment Guidelines, No. 14v lymph nodes (along the root of the superior mesenteric vein) are again defined as loco-regional lymph nodes, and it is clarified that distal gastric cancer presenting with infra-pyloric regional lymph node (No.6) metastasis is recommended for D2+ superior mesenteric vein (No. 14v) lymph node dissection. To explore the relevance and clinical significance of No.6 and No.14v lymphadenectomy in radical gastric cancer surgery, a review of the national and international literature revealed that No.6 lymph node metastasis was associated with No.14v lymph node metastasis, that No.6 lymph node status was a valid predictor of No.14v lymph node negative status and false negative rate, and that for gastric cancer patients with No. 14v lymph node negative and No.6 lymph node positive, the dissection of No.14v lymph node may also have some significance. The addition of No. 14v lymph node dissection in radical gastrectomy is safe, but it is more important to distinguish the patients who can benefit from it. Professor Liang Han of Tianjin Medical University Cancer Hospital is currently leading a multicenter, large-sample, prospective clinical trial (NCT02272894) in China, which is expected to provide higher level evidence for the clinical significance of lymph node dissection in No.14v.

Stem Cell and Exosome Therapy in Pulmonary Hypertension

Pulmonary hypertension is a rare and progressive illness with a devastating prognosis. Promising research efforts have advanced the understanding and recognition of the pathobiology of pulmonary hypertension. Despite remarkable achievements in terms of improving the survival rate, reducing disease progression, and enhancing quality of life, pulmonary arterial hypertension (PAH) is not completely curable. Therefore, an effective treatment strategy is still needed. Recently, many studies of the underlying molecular mechanisms and technological developments have led to new approaches and paradigms for PAH treatment. Management based on stem cells and related paracrine effects, epigenetic drugs and gene therapies has yielded prospective results for PAH treatment in preclinical research. Further trials are ongoing to optimize these important insights into clinical circumstances.

Clinical manifestations and gene analysis of 18 cases of hereditary protein S deficiency / 中华血液学杂志

Objective: To analyze the clinical manifestations and molecular pathogenesis of 18 patients with inherited protein S (PS) deficiency. Methods: Eighteen patients with inherited PS deficiency who were admitted to the Institute of Hematology & Blood Diseases Hospital from June 2016 to February 2019 were analyzed: activity of protein C (PC) and antithrombin (AT) , PS activity were measured for phenotype diagnosis; high throughput sequencing (HTS) was used for screening of coagulation disease-related genes; Sanger sequencing was used to confirm candidate variants; Swiss-model was used for three-dimensional structure analysis. Results: The PS:C of 18 patients ranged from 12.5 to 48.2 U/dL. Among them, 16 cases developed deep vein thrombosis, including 2 cases each with mesenteric vein thrombosis and cerebral infarction, and 1 case each with pulmonary embolism and deep vein thrombosis during pregnancy. A total of 16 PROS1 gene mutations were detected, and 5 nonsense mutations (c.134_162del/p.Leu45*, c.847G>T/p.Glu283*, c.995_996delAT/p.Tyr332*, c.1359G> A/p.Trp453*, c.1474C>T/p.Gln492*) , 2 frameshift mutations (c.1460delG/p.Gla487Valfs*9 and c.1747_1750delAATC/p.Asn583Wfs*9) and 1 large fragment deletion (exon9 deletion) were reported for the first time. In addition, the PS:C of the deep vein thrombosis during pregnancy case was 55.2 U/dL carrying PROC gene c.565C>T/p.Arg189Trp mutation. Conclusion: The newly discovered gene mutations enriched the PROS1 gene mutation spectrum which associated with inherited PS deficiency.

Tat-functionalized Ag-FeO nano-composites as tissue-penetrating vehicles for tumor magnetic targeting and drug delivery

In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide (Tat), producing Tat-modified Ag-FeO nanocomposites (Tat-FeAgNPs). To load drugs, an -SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin (Dox) in a pH-sensitive pattern. The delivery efficiency of this system was assessed using MCF-7 cells, and using null BalB/c mice bearing MCF-7 xenograft tumors. Our results demonstrated that both Tat and externally applied magnetic field could promote cellular uptake and consequently the cytotoxicity of doxorubicin-loaded nanoparticles, with the IC of Tat-FeAgNP-Dox to be 0.63 µmol/L. The delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the optical imaging tests, in which Tat-FeAgNP-Cy5 yielded the most efficient accumulation in the tumor (6.7±2.4% ID of Tat-FeAgNPs). Anti-tumor assessment also demonstrated that Tat-FeAgNP-Dox displayed the most significant tumor-inhibiting effects and reduced the specific growth rate of tumor by 29.6% ( = 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.

Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides

Brain delivery of macromolecular therapeutics (e.g., proteins) remains an unsolved problem because of the formidable blood-brain barrier (BBB). Although a direct pathway of nose-to-brain transfer provides an answer to circumventing the BBB and has already been intensively investigated for brain delivery of small drugs, new challenges arise for intranasal delivery of proteins because of their larger size and hydrophilicity. In order to overcome the barriers and take advantage of available pathways (e.g., epithelial tight junctions, uptake by olfactory neurons, transport into brain tissues, and intra-brain diffusion), a low molecular weight protamine (LMWP) cell-penetrating peptide was utilized to facilitate nose-to-brain transport. Cell-penetrating peptides (CPP) have been widely used to mediate macromolecular delivery through many kinds of biobarriers. Our results show that conjugates of LMWP-proteins are able to effectively penetrate into the brain after intranasal administration. The CPP-based intranasal method highlights a promising solution for protein therapy of brain diseases.

exploratory analysis of dynamic change of metabolic syndrome in relation to the risk of developing cardiovascular disease in a Chinese cohort

Metabolic syndrome [MS] is the syndrome closely related to cardiovascular disease [CVD] risk factors. Few prospective studies have compared the impact of dynamic changes of MS on the development of cardiovascular diseases [CVD]. Overall, 3461 subjects were recruited from a cohort study on Prevention of Multiple Metabolic disorders and MS in Jiangsu of China [PMMJS] with a follow up of 3.8 years. The associations between the dynamic changes [Difference, the value at first follow-up subtract the value at baseline] of MS, component numbers, components and relative risk [RR] of CVD were analyzed by using Cox regression model. The total incidence standardized rate of CVD was 2.58%,and the incidence standardized rates of CVD in MS-/follow-up MS-,baseline MS-/follow-up MS+, baseline MS+/follow-up MS- and baseline MS+/follow-up groups were 2.05%,5.01%,1.65% and 4.39% separately. After adjustment confounding factors Difference in FPG, BP and TG have significantly effects on the incidence of CVD. Difference of MS component numbers had the prediction ability of CVD, but MS groups based on baseline and first follow-up MS and/or non-MS had not. In Chinese, the dynamic change of MS component numbers was a useful predict factor for CVD

Interactions of complement proteins C1q and factor H with lipid A and Escherichia coli: further evidence that factor H regulates the classical complement pathway

Proteins of the complement system are known to interact with many charged substances. We recently characterized binding of C1q and factor H to immobilized and liposomal anionic phospholipids. Factor H inhibited C1q binding to anionic phospholipids, suggesting a role for factor H in regulating activation of the complement classical pathway by anionic phospholipids. To extend this finding, we examined interactions of C1q and factor H with lipid A, a well-characterized activator of the classical pathway. We report that C1q and factor H both bind to immobilized lipid A, lipid A liposomes and intact Escherichia coli TG1. Factor H competes with C1q for binding to these targets. Furthermore, increasing the factor H: C1q molar ratio in serum diminished C4b fixation, indicating that factor H diminishes classical pathway activation. The recombinant forms of the Cterminal, globular heads of C1q A, B and C chains bound to lipid A and E. coli in a manner qualitatively similar to native C1q, confirming that C1q interacts with these targets via its globular head region. These observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain targets. This is distinct from its role as an alternative pathway down-regulator. We suggest that under physiological conditions, factor H may serve as a downregulator of bacterially-driven inflammatory responses, thereby fine-tuning and balancing the inflammatory response in infections with Gram-negative bacteria.

Electrogenic capabilities of gram negative and gram positive bacteria in microbial fuel cell combined with biological wastewater treatment

The voltage and the power production of two gram negative and two gram positive bacteria in four identical continuous flow microbial fuel cells combined with biological wastewater treatment units were evaluated and compared in the present study. Each microbial fuel cell and biological treatment unit was operated at four different flow rates and four different external load resistances. The results show that overall removal efficiency of chemical oxygen demand for all four systems can reach more than 85.5%. Each pure culture has different power generation performance that can be affected by some factors, such as wastewater characteristics, influent flow rate, and hydraulic retention time of reactor. Good linear relationships between the flow rate and the potential and between the flow rate and the power density on four pure cultures at different external load resistances were found. Comamonas testosteroni has better power generation performance than Arthrobacter polychromogenes, especially at higher flow rate. Although Pseudomonas putida also showed higher power generation than Corynebacterium glutamicum, the difference was not statistically significant. It seems that gram negative bacteria could display higher power generation than gram positive bacteria at higher flow rate. However, more evidence is required to provide stronger proof for the difference of power generation between gram negative and gram positive bacteria

Preliminary investigation of chloramphenicol in fish, water and sediment from freshwater aquaculture pond

Analytical methods of chloramphenicol in the aquaculture environment have been developed using high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry. The contents of chloramphenicol were determined using high-performance liquid chromatography for sediment and liquid chromatography-tandem mass spectrometry for fish and water collected from a freshwater aquaculture pond in China. Chloramphenicol in the water and sediment were 112.3 ng/L and 0.1957 mg/kg, respectively. The chloramphenicol residues in 3 kinds of fish, including carp, chub and grass carp were different. Only the muscle and head of grass carp were under the minimum required performance limit [0.3 micro g/kg] and were safe to eat. The chloramphenicol in other tissues of grass carp, carp and chub exceeded the minimum required performance limit. The highest content of chloramphenicol was in the branchia of carp and the lowest was in the head of grass carp. The results showed the chloramphenicol in the aquaculture environment was serious, although the government of China had banned the use of chloramphenicol in aquaculture a few years ago

Chemical speciation of fine particle bound trace metals

This study reported quantifications of fine particle bound trace metals and their potential health risks for residents in Guangzhou, a rapidly developing and most populated city in South China. The fine particle samples were collected from October 29th. to November 8th. of 2006 at two different elevations in a mainly residential area and analyzed for the total concentration of aluminum, iron, zinc, lead, manganese, copper, arsenic, chromium, nickel, cadmium, molybdenum and cobalt. Results showed that the fine particle concentrations ranged from 95.8 micro g/m[3]to 194.7 micro g/m[3] at the ground and 83.3-190.0 micro g/m[3] on the roof, which were much higher than the 24 h fine particle standard [35 micro g/m[3]] recommended by USEPA. The total concentrations of zinc, lead, arsenic, chromium and cadmium in fine particle were 504.8, 201.6, 24.3, 7.7 and 4.4 ng/m[3], respectively, which were comparable to other major cities of China, but much higher than major cities outside of China. A sequential extraction procedure was used to fractionate these fine particle bound metals into four different fractions. Results indicated that most toxic metals were mainly distributed in bioavailable fractions. For instance, about 91% of cadmium, 85% of lead and 74% of arsenic were in bioavailable forms. Risk calculations with a simple exposure assessment model showed that the cancer risks of the bioavailable fractions of arsenic, chromium and cadmium were 3 to 33 times greater than usual goal, indicating serious health risks to the residents in this urban area